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| | <StructureSection load='2qzx' size='340' side='right'caption='[[2qzx]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='2qzx' size='340' side='right'caption='[[2qzx]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qzx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_11006_[[candida_stellatoidea]] Atcc 11006 [[candida stellatoidea]]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QZX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qzx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans Candida albicans] and [https://en.wikipedia.org/wiki/Streptomyces_argenteolus_subsp._toyonakensis Streptomyces argenteolus subsp. toyonakensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QZX FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=IVA:ISOVALERIC+ACID'>IVA</scene>, <scene name='pdbligand=STA:STATINE'>STA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IVA:ISOVALERIC+ACID'>IVA</scene>, <scene name='pdbligand=STA:STATINE'>STA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qzw|2qzw]]</div></td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Candidapepsin Candidapepsin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.24 3.4.23.24] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qzx OCA], [https://pdbe.org/2qzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qzx RCSB], [https://www.ebi.ac.uk/pdbsum/2qzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qzx ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qzx OCA], [https://pdbe.org/2qzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qzx RCSB], [https://www.ebi.ac.uk/pdbsum/2qzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qzx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CARP5_CANAL CARP5_CANAL]] Secreted aspartic peptidases (SAPs) are a group of ten acidic hydrolases considered as key virulence factors. These enzymes supply the fungus with nutrient amino acids as well as are able to degrade the selected host's proteins involved in the immune defense. During infection, plays an important role in penetration into deeper tissues and interaction with host defense. Moreover, acts toward human hemoglobin though limited proteolysis to generate a variety of antimicrobial hemocidins, enabling to compete with the other microorganisms of the same physiological niche using the microbicidal peptides generated from the host protein.<ref>PMID:11478679</ref> <ref>PMID:23927842</ref>
| + | [https://www.uniprot.org/uniprot/CARP5_CANAL CARP5_CANAL] Secreted aspartic peptidases (SAPs) are a group of ten acidic hydrolases considered as key virulence factors. These enzymes supply the fungus with nutrient amino acids as well as are able to degrade the selected host's proteins involved in the immune defense. During infection, plays an important role in penetration into deeper tissues and interaction with host defense. Moreover, acts toward human hemoglobin though limited proteolysis to generate a variety of antimicrobial hemocidins, enabling to compete with the other microorganisms of the same physiological niche using the microbicidal peptides generated from the host protein.<ref>PMID:11478679</ref> <ref>PMID:23927842</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Candidapepsin]] | + | [[Category: Candida albicans]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Borelli, C]] | + | [[Category: Streptomyces argenteolus subsp. toyonakensis]] |
| - | [[Category: Huber, R]] | + | [[Category: Borelli C]] |
| - | [[Category: Lee, J H]] | + | [[Category: Huber R]] |
| - | [[Category: Maskos, K]] | + | [[Category: Lee JH]] |
| - | [[Category: Ruge, E]] | + | [[Category: Maskos K]] |
| - | [[Category: Aspartic proteinase]]
| + | [[Category: Ruge E]] |
| - | [[Category: Aspartyl protease]]
| + | |
| - | [[Category: Candida albican]]
| + | |
| - | [[Category: Cleavage on pair of basic residue]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| Structural highlights
Function
CARP5_CANAL Secreted aspartic peptidases (SAPs) are a group of ten acidic hydrolases considered as key virulence factors. These enzymes supply the fungus with nutrient amino acids as well as are able to degrade the selected host's proteins involved in the immune defense. During infection, plays an important role in penetration into deeper tissues and interaction with host defense. Moreover, acts toward human hemoglobin though limited proteolysis to generate a variety of antimicrobial hemocidins, enabling to compete with the other microorganisms of the same physiological niche using the microbicidal peptides generated from the host protein.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Proteolytic activity is an important virulence factor for Candida albicans (C. albicans). It is attributed to the family of the secreted aspartic proteinases (Saps) from C. albicans with a minimum of 10 members. Saps show controlled expression and regulation for the individual stages of the infection process. Distinct isoenzymes can be responsible for adherence and tissue damage of local infections, while others cause systemic diseases. Earlier, only the structures of Sap2 and Sap3 were known. In our research, we have now succeeded in solving the X-ray crystal structures of the apoenzyme of Sap1 and Sap5 in complex with pepstatin A at 2.05 and 2.5 A resolution, respectively. With the structure of Sap1, we have completed the set of structures of isoenzyme subgroup Sap1-3. Of subgroup Sap4-6, the structure of the enzyme Sap5 is the first structure that has been described up to now. This facilitates comparison of structural details as well as inhibitor binding modes among the different subgroup members. Structural analysis reveals a highly conserved overall secondary structure of Sap1-3 and Sap5. However, Sap5 clearly differs from Sap1-3 by its electrostatic overall charge as well as through structural conformation of its entrance to the active site cleft. Design of inhibitors specific for Sap5 should concentrate on the S4 and S3 pockets, which significantly differ from Sap1-3 in size and electrostatic charge. Both Sap1 and Sap5 seem to play a major part in superficial Candida infections. Determination of the isoenzymes' structures can contribute to the development of new Sap-specific inhibitors for the treatment of superficial infections with a structure-based drug design program. Proteins 2008. (c) 2008 Wiley-Liss, Inc.
X-ray structures of Sap1 and Sap5: Structural comparison of the secreted aspartic proteinases from Candida albicans.,Borelli C, Ruge E, Lee JH, Schaller M, Vogelsang A, Monod M, Korting HC, Huber R, Maskos K Proteins. 2008 Apr 2;. PMID:18384081[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schaller M, Januschke E, Schackert C, Woerle B, Korting HC. Different isoforms of secreted aspartyl proteinases (Sap) are expressed by Candida albicans during oral and cutaneous candidosis in vivo. J Med Microbiol. 2001 Aug;50(8):743-7. PMID:11478679
- ↑ Bochenska O, Rapala-Kozik M, Wolak N, Bras G, Kozik A, Dubin A, Aoki W, Ueda M, Mak P. Secreted aspartic peptidases of Candida albicans liberate bactericidal hemocidins from human hemoglobin. Peptides. 2013 Oct;48:49-58. doi: 10.1016/j.peptides.2013.07.023. Epub 2013 Aug, 6. PMID:23927842 doi:http://dx.doi.org/10.1016/j.peptides.2013.07.023
- ↑ Borelli C, Ruge E, Lee JH, Schaller M, Vogelsang A, Monod M, Korting HC, Huber R, Maskos K. X-ray structures of Sap1 and Sap5: Structural comparison of the secreted aspartic proteinases from Candida albicans. Proteins. 2008 Apr 2;. PMID:18384081 doi:10.1002/prot.22021
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